# The role of gut homing receptors in congenital CMV brain infections

> **NIH NIH R21** · CORNELL UNIVERSITY · 2020 · $188,227

## Abstract

Project Summary / Abstract
Cytomegalovirus (CMV) remains the most common congenital infection and leading cause of birth defects in
children in the United States. The major target of congenital CMV is the brain, with clinical manifestations
including mental retardation, vision impairment, and sensorineural hearing loss. However, the mechanisms of
injury and immune protection in the brain during CMV infections are currently not known. Previous work has
demonstrated that CD8+ T cells play an integral role in the clearance of CMV in the brain, but how these cells
are recruited and maintained remains poorly understood. To fill this critical gap in our knowledge, we
employed a mouse model of congenital CMV and performed a detailed analysis of CMV-specific CD8+ T cell
homing to the brain. Surprisingly, the preliminary data suggests, for the first time, that the CMV-infected brain
may be using similar mechanisms of CD8+ T cell homing as the small intestine. In the gut, retinoic acid
induces the expression of the chemokine receptor CCR9 on lymphocytes, which binds to the CCL25
chemokine produced by intestinal epithelial cells. Similarly, we found that CCR9 was preferentially upregulated
on CD8+ T cells trafficking to the brain after persistent CMV infection, and both retinoic acid and CCL25 were
expressed in the choroid plexus. Based on this data, we hypothesize that interactions of CCR9 and CCL25
regulate the inflammatory immune response in the brain after congenital CMV infection. To test our
hypothesis, we will first use CCR9 KO mice to determine whether CD8+ T cells exhibit any defects in
migration, survival, or immune protection in the brain during infection. Then, we will use mice that express a
dominant negative retinoic acid receptor (dnRAR) in lymphocytes to determine whether retinoic acid is involved
in regulating expression of CCR9 and homing of CD8+ T cells to the MCMV-infected brain. Knowledge gained
from these studies will provide the necessary framework for developing novel diagnostics and therapeutics for
the treatment of congenital CMV disease.

## Key facts

- **NIH application ID:** 9836798
- **Project number:** 5R21AI142382-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Brian David Rudd
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,227
- **Award type:** 5
- **Project period:** 2018-12-11 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836798

## Citation

> US National Institutes of Health, RePORTER application 9836798, The role of gut homing receptors in congenital CMV brain infections (5R21AI142382-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9836798. Licensed CC0.

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